Integrated growth assessment in the first 1000 d of life: an interdisciplinary conceptual framework.

OBJECTIVES: Prenatal growth affects short- and long-term morbidity, mortality and growth, yet communication between prenatal and postnatal healthcare teams is often minimal. This paper aims to develop an integrated, interdisciplinary framework for foetal/infant growth assessment, contributing to the continuity of care across the first 1000 d of life. DESIGN: A multidisciplinary think-tank met regularly over many months to share and debate their practice and research experience related to foetal/infant growth assessment. Participants' personal practice and knowledge were verified against and supplemented by published research. SETTING: Online and in-person brainstorming sessions of growth assessment practices that are feasible and valuable in resource-limited, low- and middle-income country (LMIC) settings. PARTICIPANTS: A group of obstetricians, paediatricians, dietitians/nutritionists and a statistician. RESULTS: Numerous measurements, indices and indicators were identified for growth assessment in the first 1000 d. Relationships between foetal, neonatal and infant measurements were elucidated and integrated into an interdisciplinary framework. Practices relevant to LMIC were then highlighted: antenatal Doppler screening, comprehensive and accurate birth anthropometry (including proportionality of weight, length and head circumference), placenta weighing and incorporation of length-for-age, weight-for-length and mid-upper arm circumference in routine growth monitoring. The need for appropriate, standardised clinical records and corresponding policies to guide clinical practice and facilitate interdisciplinary communication over time became apparent. CONCLUSIONS: Clearer communication between prenatal, perinatal and postnatal health care providers, within the framework of a common understanding of growth assessment and a supportive policy environment, is a prerequisite to continuity of care and optimal health and development outcomes.

Association of Prenatal Placental Function with Anthropometry and Body Composition through 2 years of Age in South African Infants: The UmbiBaby Study.

BACKGROUND: Placental insufficiency negatively impacts fetal growth and body composition (BC), potentially affecting lifelong health. Placental insufficiency, detectable as an abnormal umbilical artery resistance index (UmA-RI) on Doppler ultrasonography, is highly prevalent in otherwise healthy South African pregnant women. Appropriate intervention reduces stillbirth and perinatal death, but research on long-term outcomes of surviving infants is lacking. OBJECTIVES: This study aimed to describe and compare anthropometry and BC during the first 2 y of life in a cohort of term-born infants with normal and abnormal prenatal UmA-RI. METHODS: Term-born infants (n = 81; n = 55 normal, n = 26 abnormal UmA-RI on third trimester Doppler screening) were followed up at 8-time points until age 2 y. Anthropometric measurements were taken, and FFM and FM were assessed by deuterium dilution. Age- and sex-specific z-scores were calculated for anthropometric indices, FM, FFM, FM index (FMI), and FFM index (FFMI) using appropriate reference data. Anthropometry and BC of infants with normal and abnormal UmA-RI were compared using an independent t-test or Mann-Whitney test. RESULTS: At most ages, group mean z-scores were <0 for length-for-age and FM and >0 for weight-for-length and FFM. Compared with infants with normal UmA-RI, infants with abnormal UmA-RI had significantly lower weight-for-age z-scores at birth (-0.77 ± 0.75 compared with -0.30 ± 1.10, P = 0.026), ages 10 wk to 9 mo (-0.4 ± 0.87 to -0.2 ± 1.12 compared with 0.3 ± 0.85 to 0.6 ± 1.09; P = 0.007-0.017) and 18 mo (-0.6 ± 0.82 compared with 0.1 ± 1.18; P = 0.037); length-for-age z-scores at ages ≤14 wk (-1.3 ± 1.25 to -0.9 ± 0.87 compared with -0.2 ± 1.04 to -0.1 ± 1.00; P = 0.004-0.021); and FFM-for-age z-scores at ages ≤9 mo (-0.1 ± 0.82 to 0.7 ± 0.71 compared with 0.7 ± 1.00 to 1.3 ± 0.85; P = 0.002-0.028). FFMI, percentage FFM, FM, percentage FM, and FMI showed no consistent significant differences. CONCLUSIONS: Infants with abnormal UmA-RI had lower weight-for-age and length-for-age z-scores, particularly at younger ages, with proportionally lower FFM but no consistent differences in percentage FFM and FFMI. These findings merit further investigation in larger cohorts.

A novel screening tool to predict severe acute malnutrition through automated monitoring of weight-for-age growth curves.

Weight-for-age (WFA) growth faltering often precedes severe acute malnutrition (SAM) in children, yet it is often missed during routine growth monitoring. Automated interpretation of WFA growth within electronic health records could expedite the identification of children at risk of SAM. This study aimed to develop an automated screening tool to predict SAM risk from WFA growth, and to determine its predictive ability compared with simple changes in weight or WFA z-score. To develop the screening tool, South African child growth experts (n = 30) rated SAM risk on 100 WFA growth curves, which were then used to train an artificial neural network (ANN) to assess SAM risk from consecutive WFA z-scores. The ANN was validated in 185 children under five (63 SAM cases; 122 controls) using diagnostic accuracy methodology. The ANN's performance was compared with that of changes in weight or WFA z-score. Even though experts' SAM risk ratings of the WFA growth curves differed considerably, the ANN achieved a sensitivity of 73.0% (95% confidence interval [CI]: 60.3; 83.4), specificity of 86.1% (95% CI: 78.6; 91.7) and receiver-operating characteristic curve area of 0.795 (95% CI: 0.732; 0.859) during validation with real cases, outperforming changes in weight or WFA z-scores. The ANN, as an automated screening tool, could markedly improve the identification of children at risk of SAM using routinely collected WFA growth information.

Understanding the Impact of Maternal HIV Infection on the Health and Well-Being of Mothers and Infants in South Africa: Siyakhula Collaborative Workshop Report.

The Siyakhula study is an ongoing, observational cohort study in Pretoria, South Africa, that aims to understand how maternal HIV infection and perinatal environmental factors shape development and health in infants who are HIV-exposed (in utero and during breastfeeding) but remain uninfected themselves (HEU). The Siyakhula Collaborative Workshop, which took place at the Research Centre for Maternal, Fetal, Newborn & Child Health Care Strategies at Kalafong Hospital in Pretoria, South Africa on November 15-16, 2018, brought together a group of international health scientists, clinicians, and stakeholders, including women with lived experience, to build capacity for research and training on the impact of HIV infection on women's and infants' health across geographical and disciplinary boundaries. The workshop sought to summarise the state of knowledge on the effects of being HEU on infant development and health in the first two years of life, identify gaps in existing research on modifiable exposures that may be associated with poor infant development, and develop ideas for novel research and interventions to lessen or prevent adverse health outcomes in pregnant or breastfeeding people living with HIV. These proceedings summarise the pre-workshop consensus process that was used to identify priority areas to discuss during small-group breakout sessions, as well as the themes and key challenges that emerged from these discussions during the workshop.

Mother-to-child transmission of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in HIV-infected pregnant women in South Africa.

BACKGROUND: Sexually transmitted infections (STIs) can be transmitted from mother to neonate. We determined the frequency of mother-to-child transmission (MTCT) of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis to the newborn nasopharynx. METHODS: This study was nested in a cohort study of etiologic testing versus syndromic management for STIs among pregnant women living with human immunodeficiency virus in South Africa. Mothers were tested for STIs using the GeneXpert platform within 60 days after delivery. Nasopharyngeal swabs were obtained from newborns of mothers with a positive STI test; these were then tested by Xpert® on the same day based on the maternal STI diagnosis. RESULTS: We tested nasopharyngeal swabs from 85 STI-exposed newborns; 74 (87%) were tested within 2 weeks after birth (median five; range 2-12 days). MTCT frequency of any STI was 30/74 (41%); 43% (23/53) for C. trachomatis, 29% (2/7) for N. gonorrhoeae, and 24% (6/25) for T. vaginalis. Also, 4/11 (36%) swabs obtained between 14 and 60 days after delivery tested positive for STI. CONCLUSIONS: There was a high frequency of MTCT of STIs to the nasopharynx of newborns in our setting. The impact of nasopharyngeal colonization and the benefits of STI testing on newborn health remain to be determined.

Does in utero HIV exposure and the early nutritional environment influence infant development and immune outcomes? Findings from a pilot study in Pretoria, South Africa.

BACKGROUND: As mother-to-child transmission of HIV decreases, and the population of infants who are born HIV-exposed, but uninfected (HEU) continues to rise, there is a growing need to understand the development and health outcomes of infants who are HEU to ensure that they have the healthiest start to life. METHODS: In a prospective cohort pilot study at Kalafong Hospital, Pretoria, South Africa, we aimed to determine if we could recruit new mothers living with HIV on antiretrovirals (ART; n = 20) and not on ART (n = 20) and new mothers without HIV (n = 20) through our clinics to study the effects of HEU on growth and immune- and neurodevelopment in infants in early life, and test the hypothesis that infants who were HEU would have poorer health outcomes compared to infants who were HIV-unexposed, uninfected (HUU). We also undertook exploratory analyses to investigate relationships between the early nutritional environment, food insecurity and infant development. Infant growth, neurodevelopment (Guide for Monitoring Child Development [GMCD]) and levels of monocyte subsets (CD14, CD16 and CCR2 expression [flow cytometry]) were measured in infants at birth and 12 weeks (range 8-16 weeks). RESULTS: We recruited 33 women living with HIV on ART and 22 women living without HIV within 4 days of delivery from June to December 2016. Twenty-one women living with HIV and 10 without HIV returned for a follow-up appointment at 12 weeks postpartum. The high mobility of this population presented major challenges to participant retention. Preliminary analyses revealed lower head circumference and elevated CCR2+ (% and median fluorescence intensity) on monocytes at birth among infants who were HEU compared to HUU. Maternal reports of food insecurity were associated with lower maternal nutrient intakes at 12 weeks postpartum and increased risk of stunting at birth for infants who were HEU, but not infants who were HUU. CONCLUSIONS: Our small feasibility pilot study suggests that HEU may adversely affect infant development, and further, infants who are HEU may be even more vulnerable to the programming effects of suboptimal nutrition in utero and postnatally. This pilot and preliminary analyses have been used to inform our research questions and protocol in our ongoing, full-scale study.

OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories.

BACKGROUND: HIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels. METHODS: The oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 specimens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results. FINDINGS: HIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 ±â€¯0.3% specificity and 98.2 ±â€¯0.9% sensitivity, and compared to high-sensitivity assays, 99.6 ±â€¯0.6% specificity and 86.2 ±â€¯2.5% sensitivity, with 2.6 ±â€¯0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (<4 h vs. 35-72 h). Forty-one untrained volunteers blindly tested two specimens each with 96.8 ±â€¯0.8% accuracy. INTERPRETATION: OLA-Simple compares favorably with HIVDR genotyping by Sanger and sensitive comparators. Instructional software enabled inexperienced, first-time users to perform the assay with high accuracy. The reduced complexity, cost, and training requirements of OLA-Simple could improve access to HIVDR testing in low-resource settings and potentially allow same-day selection of appropriate antiretroviral therapy. FUND: USA National Institutes of Health R01; the Clinical and Retrovirology Research Core and the Molecular Profiling and Computational Biology Core of the UW CFAR; Seattle Children's Research Institute; UW Holloman Innovation Challenge Award; Pilcher Faculty Fellowship.

Gingival Recession and Localized Aggressive Periodontitis Among HIV-infected Children and Adolescents Receiving Antiretroviral Therapy.

BACKGROUND: Limited information is available on gingival recession or localized aggressive periodontitis among HIV-infected children and adolescents. This study reports on the prevalence of these conditions among children and adolescents receiving antiretroviral therapy (ART). METHODS: A cross-sectional study on HIV-infected children and adolescents attending a Pediatric HIV clinic in Gauteng, South Africa, between January 2013 and June 2016. Patients received an oral examination and oral hygiene instructions, irrespective of oral- or dental-related complaints. Hard and soft tissue pathology was managed and recorded, together with relevant demographic and clinical data. Statistical analysis was performed in Stata 14 with P < 0.05 as significant. RESULTS: A total of 554 children and adolescents 5-19 years of age (median age: 12.2 years; interquartile range: 10.3-14.9) were included, of whom 78 (14.1%) presented with gingival recession on permanent mandibular incisors and/or localized aggressive periodontitis of molar teeth. Multivariable logistic regression revealed that patients with gingival recession and aggressive periodontitis had a significantly shorter duration of ART and were more likely to have suboptimal HIV control (CD4 count ≤500 cells/µL and/or HIV viral load ≥50 copies/mL) and be on advanced ART regimens after virologic failure on first- and second-line treatment. CONCLUSIONS: The results emphasize the importance of oral health care among HIV-infected children and adolescents from the onset, to prevent and manage conditions that could result in tooth loss and permanent disfigurement. This is of particular importance in the presence of virologic failure and immunosuppression.

Persistence of HIV drug resistance among South African children given nevirapine to prevent mother-to-child-transmission.

OBJECTIVES: We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside reverse transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT). DESIGN: A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa. METHODS: Children referred for initiation of antiretroviral therapy (ART) were enrolled from July 2010 through February 2013. HIV drug resistance testing was performed using the oligonucleotide ligation assay (OLA) on dried blood spots (DBS) collected at enrolment and monthly follow-up visits for 2 years. RESULTS: South African children who failed HIV-prophylaxis had a high prevalence of NNRTI-resistant HIV (46/88; 52%). Among children with NNRTI-resistance, the frequency of the predominant resistant variant in each child's HIV-quasispecies was high (median 96%) at study entry (median age 7.5 months), and in 26 out of 27 followed a median of 13 months persisted at a high frequency (median 89%). CONCLUSION: Our finding that infants who fail HIV-prophylaxis frequently have long-lived NNRTI-resistant HIV suggests that resistance will likely persist through 36 months of age, when children qualify for NNRTI-based ART. These children may benefit from HIV drug resistance testing to guide selection of their treatment.

Growth in HIV-infected children on long-term antiretroviral therapy.

OBJECTIVES: To describe growth in HIV-infected children on long-term antiretroviral therapy (ART) and to assess social, clinical, immunological and virological factors associated with suboptimal growth. METHODS: This observational cohort study included all HIV-infected children at an urban ART site in South Africa who were younger than 5 years at ART initiation and with more than 5 years of follow-up. Growth was assessed using weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores (BAZ). Children were stratified according to pre-treatment anthropometry and age. Univariate and mixed linear analysis were used to determine associations between independent variables and weight and height outcomes. RESULTS: The majority of the 159 children presented with advanced clinical disease (90%) and immunosuppression (89%). Before treatment underweight, stunting and wasting were common (WAZ<-2 = 50%, HAZ<-2 = 73%, BAZ<-2 = 19%). Weight and BMI improved during the initial 12 months, while height improved over the entire 5-year period. Height at study exit was significantly worse for children with growth impairment at ART initiation (P < 0.001), and infants (<1 year) demonstrated superior improvement in terms of BMI (P = 0.04). Tuberculosis was an independent risk factor for suboptimal weight (P = 0.01) and height (P = 0.02) improvement. Weight gain was also hindered by lack of electricity (P = 0.04). Immune reconstitution and virological suppression were not associated with being underweight or stunted at study endpoint. CONCLUSIONS: Malnutrition was a major clinical concern for this cohort of HIV-infected children. Early ART initiation, tuberculosis co-infection management and nutritional interventions are crucial to ensure optimal growth in HIV-infected children.

Early diagnosis is critical to ensure good outcomes in HIV-infected children: outlining barriers to care.

HIV-infected children require early initiation of antiretroviral therapy (ART) to ensure good outcomes. The aim was to investigate missed opportunities in childhood HIV diagnosis leading to delayed ART initiation. Baseline data were reviewed of all children aged <15 years referred over a 1-year period for ART initiation to the Kalafong Hospital HIV services in Gauteng, South Africa. Of the 250 children, one-quarter (24.5%) was of school-going age, 34.5% in the preschool group, 18% between 6 and 12 months old and 23% below 6 months of age (median age = 1.5 years [interquartile range 0.5-4.8]). Most children (82%) presented with advanced/severe HIV disease, particularly those aged 6-12 months (95%). Malnutrition was prominent and referrals were mostly from hospital inpatient services (61%). A structured caregiver interview was conducted in a subgroup, with detailed review of medical records and HIV results. The majority (≥89%) of the 65 interviewed caregivers reported good access to routine healthcare, except for postnatal care (26%). Maternal HIV-testing was mostly done during the second and third pregnancy trimesters (69%). Maternal non-disclosure of HIV status was common (63%) and 83% of mothers reported a lack of psychosocial support. Routine infant HIV-testing was not done in 66%, and inadequate reporting on patient-held records (Road-to-Health Cards/Booklets) occurred frequently (74%). Children with symptomatic HIV disease were not investigated at primary healthcare in 53%, and in 68% of families the siblings were not tested. One-third of children (35%) had a previous HIV diagnosis, with 77% of caregivers aware of these prior results, while 50% acknowledged failing to attend ART services despite referral. In conclusion, a clear strategy on paediatric HIV case finding, especially at primary healthcare, is vital. Multiple barriers need to be overcome in the HIV care pathway to reach high uptake of services, of which especially maternal reasons for not attending paediatric ART services need further exploration.

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa.

OBJECTIVE: Limited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors. METHODS: Data from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis. RESULTS: The study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033). CONCLUSION: Major protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

Missing HIV prevention opportunities in South African children--a 7-year review.

BACKGROUND: The prevention of mother-to-child transmission (PMTCT) program in South Africa is now successful in ensuring HIV-free survival for most HIV-exposed children, but gaps in PMTCT coverage remain. The study objective was to identify missed opportunities for prevention of mother-to-child transmission of HIV using the four PMTCT stages outlined in National Guidelines. METHODS: This descriptive study enrolled HIV-exposed children who were below the age of 7 years and therefore born during the South African PMTCT era. The study site was in Gauteng, South Africa and enrolment was from June 2009 to May 2010. The clinical history was obtained through a structured caregiver interview and review of medical records and included socio-demographic data, medical history, HIV interventions, infant feeding information and HIV results. The study group was divided into the "single dose nevirapine" ("sdNVP") and "dual-therapy" (nevirapine & zidovudine) groups due to PMTCT program change in February 2008, with subsequent comparison between the groups regarding PMTCT steps during the preconception stage, antenatal care, labor and delivery and postpartum care. RESULTS: Two-hundred-and-one HIV-exposed children were enrolled: 137 (68%) children were HIV infected and 64 (32%) were HIV uninfected. All children were born between 2002 and 2009, with 78 (39%) in the "sdNVP" and 123 (61%) in the "dual-therapy" groups. The results demonstrate significant improvements in antenatal HIV testing and PMTCT enrolment, known maternal HIV diagnosis at delivery, mother-infant antiretroviral interventions, infant HIV-diagnosis and cotrimoxazole prophylaxis. Missed opportunities without improvement include pre-conceptual HIV-services and family planning, tuberculosis screening, HIV disclosure, psychosocial support and postnatal care. Not receiving consistent infant feeding messaging was the only PMTCT component that worsened over time. CONCLUSIONS: Multiple missed opportunities for optimal PMTCT were identified, which collectively increase children's risk of HIV acquisition. Although HIV-testing and antiretroviral interventions improved, all PMTCT components need to be optimized to reach the goal of total pediatric HIV elimination.

Recommendations for the medical evaluation of children prior to adoption in South Africa.

The current legislative framework in South Africa (SA) supports adoption as the preferred form of care for children with inadequate or no parental or family support. There are an estimated 3.8 million orphans in SA, with approximately 1.5 - 2 million children considered adoptable. As a means of improving services, newly drafted adoption guidelines from the National Department of Social Development will in future require both non-profit and private sector adoption agencies to obtain a medical report on a child prior to placement. However, no local guidelines specify what an appropriate medical examination entails or how it should be reported. For the purposes of proposing and developing such guidelines, an open forum was convened at the Institute of Pathology, University of Pretoria, in March 2013. These 'Recommendations for the medical evaluation of children prior to adoption in South Africa' emanate from this meeting.

Consequences of prior use of full-dose ritonavir as single protease inhibitor as part of combination antiretroviral regimens on the future therapy choices in HIV-1-infected children.

BACKGROUND: South African HIV-infected infants below age 6 months and children younger than 3 years on concomitant antimycobacterial treatment received full-dose ritonavir single protease inhibitor (RTV-sPI), together with 2 nucleoside reverse transcriptase inhibitors, from 2004 until 2008. Use of RTV-sPI has been described as a risk factor for PI drug resistance, but the extent of this resistance is unknown. AIM: This research assesses clinical and virological outcome of a pediatric RTV-sPI cohort at a large South African antiretroviral therapy (ART) site in a high-burden tuberculosis setting, including resistance mutations in those failing ART. METHODS: All children initiated at Kalafong hospital before December 2008, who ever received RTV-sPI-based regimens, were assessed for patient outcome, virological failure and drug resistance. HIV viral loads were done 6-monthly and HIV genotyping since 2009. RESULTS: There were 178 children who ever received RTV-sPI, with a mean age at ART initiation of 1.4 years. Of the 135 children (76%) with >6 months follow-up, 17 children (13%) never had viral suppression, whereas another 25 (18%) developed virological failure later. Nineteen of 26 children (73%) with genotypic resistance results had major PI mutations. CONCLUSIONS: Treatment failure is not a universal feature in children with prior exposure to RTV-sPI regimens, but the significant proportion (31%) with virological failure is of concern due to high prevalence of major PI- and multiclass mutations. These children currently have no treatment options in the South African public sector, highlighting the urgent need for access to alternative ART regimens to ensure improved outcomes.